Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 100 – PDD > PDD 10 and 11: Capsules > Flashcards

PDD 10 and 11: Capsules Flashcards

1
Q

What are capsules?

A

solid dosage form in which one or more medicinal and/or inert substances are enclosed within a small shell, usually prepared from gelatin (blends of type A and B)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 2 types of capsules?

A
  • hard gelatin capsules
  • soft gelatin capsules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are hard gelatin capsules?

A
  • two sections, one slipping over the other to completely surround the formulation
  • used mostly for powders or granules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are soft gelatin capsules?

A
  • made from a more flexible, plasticized gelatin film than hard gelatin capsules
  • used mostly for liquids, semi-solids, oily substances
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the advantages of hard gelatin capsules vs. tablets? (8)

A
  • patients find them easier to swallow
  • tasteless
  • easier to manufacture
  • powder-filled hard capsules allow more flexibility in dosing (important for community or hospital pharmacist)
  • allowing filling of various combinations of diverse systems
  • fast disintegration within GI tract (also a disadvantage)
  • very convenient for preliminary drug studies (phase 1), including for blinded studies
  • easy to make identifiable
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the disadvantages of hard gelatin capsules vs. tablets? (2)

A
  • overall production is slower
  • fast disintegration within GI tract (esophageal or gastric irritation, highly potent compounds) – also an advantage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Plasma Concentration vs. Time Graph

Capsules vs. Tablets

A
  • capsules: plasma concentration increases quicker
  • tablets: plasma concentration increases slower
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the sizes of hard gelatin capsules.

A
  • empty capsules are manufactured in various sizes
  • for humans, sizes range from 000 (largest) to 5 (smallest)
  • pharmacist will have to determine the size of capsule for a given prescription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the shell components of hard capsules? (5)

A
  • gelatin (or starch, hydroxypropylmethylcellulose)
  • colorants
  • opaquing agents (titanium dioxide)
  • preservatives (ie. parabens)
  • 15-18% water (30-40% initially)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is gelatin?

A

mixture of peptides and proteins of partially hydrolyzed collagen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the purpose of colorants?

A

for identification and compliance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is pharmaceutical-grade gelatin produced?

A

using collagen derived from mammals (beef bones)

  • collagen is hydrolyzed and heat-denatured, breaking apart cross-linking between adjacent triple-helices and bonds within peptide chains
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is gelatin powder?

A

heterogeneous mixture of proteins and peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the characteristics of pharmaceutical-grade gelatin.

A

improved aqueous solubility

  • insoluble in cold water (a semi-solid hydrocolloid gel forms)
  • soluble in gastric fluid, warm water, most polar solvents
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the steps of manufacturing hard capsules?

A
  • powder preparation
  • capsule (shell) preparation
  • capsule filling
  • capsule locking and sealing
  • capsule finishing (cleaning, polishing)
  • quality control – accept or reject
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Hard Capsule Powder Preparation

How is proper fill volume achieved?

A

by adding fillers and milling powders

  • ie. lactose, microcrystalline cellulose, starch
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Hard Capsule Powder Preparation

How is proper disintegration of contents achieved?

A

by adding disintegrants

  • ie. pregelatinized starch, croscarmellose, sodium starch glycolate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Hard Capsule Powder Preparation

How are free flowing contents (when caps are being filled) achieved?

A

by lubricants/glidants

  • ie. fumed silicon dioxide, stearic acid, talc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Hard Capsule Powder Preparation

What is used for proper wetting?

A

surface active agent

  • ie. Na+ lauryl SO4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Can aqueous liquids be put in hard gelatin capsules?

A

no – due to risk of leakage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Can semi-solids (like pastes) be put in hard gelatin capsules?

A

OK if the liquid component is not aqueous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Hard Capsule Shell Production

How are shells produced?

A
  • dipping of pins into a reservoir of melted gelatin mixture (includes excipients)
  • pins are lifted and rotated
  • gelatin is dried by gentle air flow that is temperature and humidity-controlled
  • bronze jaws strip the body and cap from pins
  • body and cap are transferred into collets in which they are firmly held
  • collet rotates and a knife trims the capsule piece to the desired length
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Hard Capsule Filling

A
  • compatibility with gelatin
  • automatic machines – fine particles are better
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Hard Capsule Filling

Describe manual filling.

A
  • mixing the ingredients, reducing to a fine powder (granules do not pack readily in capsules)
  • potent drugs given in small doses usually are mixed with an inert diluent (lactose)
  • the powder is usually placed on paper and flattened with spatula to about 1/3 of capsule length
  • the cap is removed and the body is pressed repeatedly into the powder until it is filled
  • the spatula is useful in pushing the last quantity of powder into the capsule
  • the cap is replaced and the capsule is weighed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Hard Capsule Filling

Describe extemporaneous manual filling machines.

A
  • entire capsules are placed in the machine by hand or using different devices
  • drug is swiped into the capsules
  • the lower plate carries a clamp which holds the capsule bases and makes it possible to remove and replace the caps
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Hard Capsule Filling

Describe semi-automatic filling machines.

A
  • same principle – separation of cap from body, filling the body half and rejoining the cap and body halves
  • powders frequently include diluents (lactose, mannitol) and lubricants (stearate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Hard Capsule Filling

Describe automatic filling machines.

A
  • same principle, larger quantities – separation of cap from body, filling the body half and rejoining the cap and body halves
  • main difference between machines is how the formulation is dosed into the capsules
  • one operator can handle more than one machine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Hard Capsule Locking

What is positive closure?

A

sealing and locking

  • helps prevent the separation of capsules during shipping and handling
29
Q

Hard Capsule Locking

Describe the capsule locking.

A

hard-gelatin capsules are made self-locking by forming indentations or grooves on the inside of the cap

  • tapered rim avoids telescoping
  • indentations prevent premature opening
  • grooves lock the two halves together once the capsule has been filled
30
Q

Hard Capsule Sealing

What are the 2 ways that hard gelatin capsules are hermetically (air-tight) sealed?

A
  • extemporaneously
  • in manufacturing
31
Q

Hard Capsule Sealing

What is extemporaneous sealing?

A

water and a cotton swab

32
Q

Hard Capsule Sealing

What are the 2 types of sealing in manufacturing?

A
  • banding
  • microspray sealling
33
Q

Hard Capsule Sealing

What is banding?

A

polymer or gelatin (often distinctively colored) band around the seam

  • currently is the single most frequently used sealing method)
34
Q

Hard Capsule Sealing

What is microspray sealing

A

water and ethanol are sprayed around the seam area, followed by thermal bonding

35
Q

Hard Capsule Cleaning

A
  • all capsules, whether they have been filled by hand or machine, will require cleaning
  • hand polishing with a cloth or gauze in a case of a small batch
  • for large quantities, rotation or shaking with crystalline sodium chloride
  • capsules are then rolled on a cloth-covered surface
36
Q

Hard Capsule Finished Product Testing

A
  • weight – batch testing
  • appearance
  • visual or electronic monitoring
  • high reject rate → evaluate process
  • fillling into containers and labeling is automated in manufacturing, and these steps are also subject to the requirements of Good Manufacturing Practice (GMP)
37
Q

Describe soft gelatin capsules.

A

soft, globular, gelatin shell that is somewhat thicker than hard gelatin capsules

38
Q

What is generally needed for the preparation and filling of soft gelatin capsules?

A

large scale production

39
Q

What shapes are soft gelatin capsules?

A

commercially filled soft gelatin capsules come in a wide choice of sizes and shapes

  • round
  • oval
  • oblong
  • tube or suppository-shaped
40
Q

How do soft gelatin capsule shells compare to hard gelatin capsule shells?

A

basic component is also gelatin, however, the shell has been plasticized by the addition of glycerin/glycerol or sorbitol (or both)

41
Q

What determines the ‘hardness’ of soft gelatin capsules?

A

ratio of dry plasticizer to dry gelatin

  • the larger the number, the softer the capsule
42
Q

Soft Gelatin Capsules

What are lower ratios (0.3-0.5) of dry plasticizer to dry gelatin used for?

A

oily vehicles

43
Q

Soft Gelatin Capsules

What are intermediate ratios (0.4-0.6) of dry plasticizer to dry gelatin used for?

A

oily vehicles that include surfactant

44
Q

Soft Gelatin Capsules

What are higher ratios of dry plasticizer to dry gelatin used for?

A

water-miscible vehicles

45
Q

Soft Gelatin Capsule Shells

What is the typical residual shell water content?

A

6-10%

46
Q

Soft Gelatin Capsule Shells

Other than gelatin (and addition of glycerin/glycerol or sorbitol), what are other components of the shell?

A
  • dyes
  • opacifiers
  • preservatives
  • flavours
47
Q

Soft Gelatin Capsule Formulation

What is it useful for formulating?

A

oil (most frequently) or other liquid substances that cannot easily be incorporated into powders

48
Q

Soft Gelatin Capsule Formulation

What might soft gelatin capsules contain?

A
  • single liquid
  • combination of miscible liquids
  • solution of a drug in a liquid or a suspension of a drug in a liquid
49
Q

Soft Gelatin Capsule Formulation

What are liquids in soft gelatin capsules limited to?

A

liquids are limited to those that do not have an adverse effect on the gelatin walls (2.5 < pH < 7.5)

  • aqueous liquids (> 5% water content) cannot be filled
  • in general, all liquids used for filling must flow by gravity at a temperature of 35ºC
50
Q

Soft Gelatin Capsule Formulation

What is the sealing temperature of gelatin film?

A

37ºC

51
Q

Soft Gelatin Capsule Formulation

Examples

A
  • long-chain and medium-chain triglyceride (vegetable oils) as a vehicle for highly lipophilic compounds
  • water insoluble vitamins
  • low volume liquid formulations (such as PEG 400, PEG 600) that accelerate dissolution of drugs
52
Q

What is EPANOVA?

A

(SEE NOTES)

  • lipid-regulating agent
  • coated soft-gelatin capsule containing 1 gram of fish oil-derived free fatty acids
53
Q

What are the compatibility and stability concerns for soft gelatin capsules?

A

there is more intimate contact between the shell and its liquid content, which increases the possibility of interactions

  • number of excipients used in soft-gelatin capsules (plasticizers, PEGs) are known to undergo auto-oxidation to form higher molecular weight aldehydes, which can lead to loss of gelatin aqueous solubility by crosslinking
  • drugs can migrate from oily vehicle to the shell
  • hygroscopic compounds may attract water, taking it from the gelatin shell
  • emulsions may release water to the gelatin shell
54
Q

What is marinol?

A

(SEE SLIDES)

55
Q

What is tetrahydrocannabinol (THC)?

A

active ingredient in marijuana that is a highly hydrophobic compound (BCS II) with extremely low bioavailability when administered orally

  • has been shown to improve appetite and to reduce nausea in terminal-stage AIDS and cancer patients
  • solubilized in sesame oil (long-chain triglycerides) which is packed into soft gelatin capsule
56
Q

Soft Gelatin Capsule Filling

What is the rotary die process?

A
  • liquid gelatin flowing from an overhead tank is formed into 2 continuous ribbons by the rotary die machine
  • gelatin ribbons are brought into convergence between the twin revolving dies and an injection wedge which injects the filling material
  • the fill material is injected between the ribbons at the moment that the twin dies form pockets in the gelatin ribbons
  • capsules are sealed by pressure and heat
  • the machine ejects the completed capsule
  • the pumps are engineered to extremely high degree of precision and accuracy
  • markings may be applied
  • waste gelatin is recycled
57
Q

Soft Gelatin Capsule Filling

What does the rotary die process allow encapsulation of?

A

heavy materials, such as ointments and pastes

58
Q

Standard Softgel Machine

A

(see slides)

59
Q

What are the advantages of soft gelatin capsules? (7)

A
  • smooth and easy to swallow
  • tasteless (good for taste masking)
  • complete sealing (for oxygen sensitive materials)
  • high accuracy and precision possible (important especially for highly potent compounds – better than hard gelation capsules)
  • for some poorly water-soluble drugs, may improve bioavailability (ie. in oils)
  • reduced dustiness, no compression stage in the manufacturing
  • can make specialty shapes (round, oval, suppository)
60
Q

What are the limitations of soft gelatin capsules? (3)

A
  • stability issue due to more contact between shell and contents – investigate interactions during formulation and stability testing
  • not appropriate for more than one kind of fill in the same capsule
  • usually more expensive to produce than hard capsules or tablets – limited number of specialty manufacturers, and problematic if even one gelatin capsule breaks during preparation because it likely contaminates nearby capsules
61
Q

Hard Capsules vs. Soft Capsules

Shell

A
  • hard: not plasticized
  • soft: plasticized – glycerin, sorbitol
62
Q

Hard Capsules vs. Soft Capsules

Manufacturing Process

A
  • hard: shells and filling are separate steps
  • soft: one step
63
Q

Hard Capsules vs. Soft Capsules

Content

A
  • hard: usually dry solids
  • soft: usually liquids/suspensions
64
Q

Hard Capsules vs. Soft Capsules

Fill Accuracy

A
  • hard: 2-5% (automated)
  • soft: 1-3%
65
Q

Hard Capsules vs. Soft Capsules

Size and Shape

A
  • hard: limited
  • soft: many
66
Q

Hard Capsules vs. Soft Capsules

Closure

A
  • hard: friction, mechanical lock, banding, liquid sealing
  • soft: hermetically sealed (heat)
67
Q

Describe capsule (both hard and soft) quality control.

A

(like with tablets)

  • disintegration
  • dissolution
  • weight variation (between 90-110%)
  • content uniformity (between 85-115% of label)
  • stability
  • moisture permeation
68
Q

Better Bioavailability of Soft Gelatin Capsules

A

in soft gelatin capsules, we can ‘package’ the drug together with solvents (ie. alcohol) and oils that are not possible with tablets or hard gelatin capsules

  • therefore the potential (and proven) better bioavailability comes from those excipients

PHRM 100 – PDD (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions